28 December 2015

Life sciences-2015

The most important biological events of 2015 according to Nature and Science

Svetlana Yastrebova, Biomolecule

So, 2015 is over. During his 365 days, we learned: there is very salty liquid water on Mars, you can't go into the river of one psychological study twice (in the sense that the same experiment gives different results from different researchers), Einstein spoke out against the interaction of elementary particles far from each other in vain, and global warming needs to be fought even more harder. In addition, humanity has set a planetary record for the number of authors of one scientific article (5154!) and photographed Pluto very well. But all this has nothing to do with the beloved science of "Biomolecule" – biology. So in this article we will analyze only those events of the year according to Science and Nature, which relate to the field of life sciences.

Some favorites of Science and Nature are the same. It is significant that the main breakthrough-2015 according to the versions of the leading scientific journals is the same. It's not hard to guess which one: CRISPR-Cas.

Breakthrough of the Year: CRISPR

A serious discussion of the system of bacterial enzymes that hits the pain points of foreign DNA and leaves pieces of the genes of its enemies for the microbe to remember began in 2012. Perhaps there is no need to retell the principle of CRISPR's work once again, since a great many articles have already been written about it. But it is worth recalling that, in addition to CRISPR, there are other ways to edit DNA: TALEN and nucleases with "zinc fingers". By the way, they, and not CRISPR, were used to treat a little girl with leukemia: "Success in the fight against leukemia: one step closer to the clinical application of genomic editing" (more about this likely miraculous healing below). Enzymes of all three of these types can be modified so that they cut DNA in strictly defined places and, if possible, do not climb into the rest. Of course, mistakes will happen sometimes, and we need to come up with ways to reduce their number.

The advantage of CRISPR over "competitors" is that this method of gene editing is simpler than others – and therefore cheaper. It does not require sophisticated equipment, and any molecular biology laboratory that wants to try CRISPR will be able to do it. This is the opinion of George Church, a Harvard professor, whose laboratory was one of the first to show the possibilities of CRISPR for editing the genome of eukaryotes.

In 2015, American scientific journals published almost twice as many scientific articles on the use of CRISPR as in 2014. Some of the works were very promising and at the same time contradictory. For example, in the spring, Chinese scientists talked about how they tried to rid the cells of discarded human embryos left over from IVF from the "bad" beta-thalassemia gene. It turned out not to be perfect (out of 86 embryos, a little more than half survived until the end of the experiment, and the necessary gene was cut out by enzymes from the cells of only four embryos), but the beginning of "editing people" was laid. Of course, there were disputes whether it was worth using an imperfect technology for research purposes (there is no question of medical ones yet), and these disputes resulted in an entire international summit on the use of genetic engineering technologies in relation to humans. The participants of the meeting came to the conclusion that while CRISPR is not stable enough to seriously consider its use for the treatment of people. This is especially true of mutations that cause hereditary diseases. We agreed that it is not worth "erasing" or changing the genes of a child before his birth in order to cure him of a hereditary disease, otherwise it is not clear what can come of it.

Although you can't approach people with your CRISPR right now, "animal editing" is allowed. By the way, for some reason the technology works much better in the case of smaller brothers. For example, in flies, CRISPR was used to obtain the desired color in 97% of cases, and in pigs, it was possible to simultaneously change the DNA sequence in 62 genes (this was done in order to eliminate some barriers to transplanting donor organs from pigs to humans).

Overall, CRISPR clearly has a great future ahead of it. Funding for research with his participation has increased dramatically over the past couple of years, as has the number of patent applications using this technology. And if it is forbidden to touch medicine yet, then CRISPR engineers will find a place to turn around in veterinary medicine, and agriculture in general. Well, and in fundamental research, of course.

Vaccination against Ebola and not only

This achievement was noted by both the editors of Science and the editors of Nature. The development of Canadian scientists during the preliminary study proved to be one hundred percent effective in the test on Guinean volunteers. This was written in the medical journal The Lancet on March 31, 2015. Of course, the acute phase of the epidemic of the ill-fated fever had ended by that time, and most of those who had to be rescued were already dead in the spring of 2015. However, the vaccine is prevention, not treatment, so it would not have helped the patients anyway. But it will help those who want to test it on themselves during the next epidemic outbreak. Ugh, ugh, ugh, of course, but regardless of our superstitions and desires, Ebola will still make itself felt.

There are diseases and older. Here is the history of the fight against malaria for many centuries, and there is still no "vaccination" against it. More precisely, the RTS vaccine has been around for a long time, but in a pilot study on 15,000 African children, it proved to be only 10% effective. However, this is better than nothing, so WHO strongly recommended starting the use of RTS in Africa.

And another good news of 2015 about contagious diseases. Despite the catastrophically low level of vaccination against polio in Ukraine, the incidence of this disease is decreasing worldwide. Nigeria sets a positive example: there were no cases of polio in the outgoing year.

Precision Medicine

And a little more about applied science. In recent years, there has been more and more talk about personalized medicine, in which each patient will have their own individual approach. The means for treatment will not least be determined by the genotype of the patient. In words, it sounds great, but in fact, doctors and biologists still have a lot of work to do in order to understand the features of the maximum number of people. Therefore, in January 2015, the President of the United States launched an initiative to allocate a grant of $ 215 million to the National Institutes of Health (NIH) so that researchers could collect data from genetic analyses, medical records and even indicators from devices like a pressure measuring device for a million volunteers across the country. Ideally, the entire received array of information should be correlated with the life history (and illness) of each individual patient. At the very least, it is necessary to discover patterns linking a person's state of health, his genes and environment. 

Analgesic yeast

Morphine is one of the most powerful painkillers, still relevant for palliative patients. This substance, as well as some other analgesics, belong to the class of opioids, and only poppies can synthesize them from living organisms. (No, of course, endogenous opioids are formed in some human cells, but they are not used as drugs.) And how nice it would be to have a backup source of such drugs!

Apparently, this source has appeared. In the summer of 2015, Science published an article describing special, bioengineered yeast. They received 21 "extra" genes, mainly from the opium poppy and its closest relatives. The change in the genotype of fungi led to the fact that they "learned" to synthesize opioids (NOT morphine) from sugars. Where are opioids, and where are carbohydrates! The structure of the molecules of the initial and final substances differ very strikingly, and therefore, until recently, in genetically modified yeast, it was possible to turn either the first or the second conditional half of the biosynthesis of opioids from carbohydrates. And finally, it was possible to combine these two halves in one yeast body.

Of course, such a discovery cannot pass by people asking questions of ethics and morality. And suddenly who will buy terrible GMO mushrooms and will not make painkillers at home, but drugs? For now, alarmists can be calm: yeast is still very bad at making opioids, and for a dozen milligrams of morphine, more than one cubic meter of nutrient fluid with yeast floating in it will be required. It is unlikely that any of the amateur dealers will be able to provide such volumes of production at home, and even be able to comply with all the technology.

Lymphatic vessels in the brain

Infections are rarely introduced directly into the brain: it is too well protected and fenced off from the fluids of the rest of the body by a blood-brain barrier. There are no lymphatic vessels and many other "manifestations" of the immune system in the brain. Well, that is, they thought so until recently. People still found lymphatic vessels and T-lymphocytes in the brain, and an article about this was published in Nature in 2015.

Not only is this discovery surprising in itself (it would seem that all blood vessels and tissue types in humans have been discovered and studied for a long time), so it may still affect the treatment of neurological diseases like multiple sclerosis, meningitis and Alzheimer's disease in the distant future. In all these pathological conditions, inflammation plays a significant role, and who knows, maybe local brain lymphocytes take part in it?

Conclusion: What's next?

Science makes an assumption in which areas it is worth waiting for discoveries in 2016. Basically, the forecast tells about the physics of elementary particles and other similar subtle matters. As for biology, then, according to the assumption of the editors of Science, we will soon find out where the faithful friends of the dog–man came from. This, of course, is not salvation from a terrible disease and not the disclosure of the global mystery of life, but it's also not bad. However, time will tell what science will achieve in the coming year.

Numerous references see in the original article – VM.

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28.12.2015

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